Research carried out on the effects of the drug Mifepristone on fruit flies and roundworms has revealed key findings that could pave the way for longer human lifespan.
Scientists at USC Dornsife College of Letters, Arts and Sciences conducted research using Drosophila, finding that the drug mifepristone can extend the lifespan of female fruit flies that have mated [1].
Longevity.Technology: Fruit flies live short lives themselves, with a lifespan of around 40 to 50 days. However, it could be that Drosophila, or the humble fruit fly, may hold the key to increasing human lifespan.
Meanwhile, in further collaborative research, scientists also discovered that mifepristone also had life-extending effects on mated roundworms called C. elegans. Mifepristone, which is also referred to as RU-486, is currently used in a number of clinical applications, including the termination of early pregnancies, as well as to treat certain types of cancer and Cushing disease.
When they mate, female fruit flies receive a sex peptide molecule from the male. Previous discoveries have indicated that this sex peptide can cause inflammation and reduce the lifespan of female fruit flies.
However, the research team, led by professor of biological sciences John Tower, including Senior Research Associate Gary Landis, were able to block the inflammatory effects of the sex peptide by giving fruit flies who mated the mifepristone drug. This resulted in reduced inflammation and longer health and lifespans for the female flies who were given the drug, when compared with a control group who did not receive mifepristone.
As fruit flies and roundworms are very different from each other, it is hoped that discovering such similar results in such distinct species could mean that this research may also have significant implications for human Longevity.
In order to better understand exactly how mifepristone works to increase lifespan, the research team studied the genes, molecules and metabolic processes which altered when the flies were given the drug. They discovered that a molecule called juvenile hormone, which plays a part in regulating development throughout the life of fruit flies, was key to the increase in lifespan.
Following mating, the sex peptide appears to move the female fruit flies’ metabolism towards processes which need more energy to maintain, which in turn leads to harmful inflammation and makes the flies more sensitive to toxins produced by bacteria.
The use of mifepristone, however, changed that process, meaning that the flies who had the drug retained healthier pathways, and ultimately lived longer lives than their counterparts who were not given mifepristone.
This builds on an earlier body of research carried out at the UCL Institute of Healthy Ageing and the Joslin Diabetes Center at Harvard Medical School which found that a combination drug treatment targeting different cellular processes in fruit flies could be an effective way to slow down the aging process. [2]
In a scientific first, Professor Tower also collaborated with Chia-An Yen PhD and Sean Curran, associate professor of gerontology and biological sciences at USC Leonard David School of Gerontology and USC Dornsife. Researchers gave mifepristone to roundworms, finding similar benefits to lifespan.
“In terms of evolution, Drosophila and C. elegans are equally as distant from each other as either one is distant from humans,” said Professor Tower, “and the fact that mifepristone can increase lifespan in both species suggests the mechanism is important to many species.”
This latest study, into the effects of inflammation, builds on a body of research into how the reduction of inflammation can have benefits for health and lifespan. For instance, researchers at the University of Kentucky have shown the type 2 diabetes drug metformin to be effective in the reparation of cells manipulated in the lab to mimic inflammation in 60-year-olds. The Florida-based firm Ponce De Leon Health is also focused on a therapy-based approach to increase healthspan by targeting factors including chronic inflammation.
Meanwhile, an Italian research team has determined that elongating telomeres, the caps at the end of each strand of DNA, may trigger anti-inflammatory activity, which could have the potential to increase health and lifespan.
Further research is now needed to build on the latest research into the use of mifepristone for life extension in fruit flies and roundworms. Scientists now need to gain a clear insight into the exact target of mifepristone in order to provide greater understanding into how this latest body of research could lay a future pathway to the extension of human health and lifespan.
[1] https://medicalxpress.com/news/2020-07-scientists-path-longer-life.html
[2] https://www.sciencedaily.com/releases/2019/09/190930161857
